Abstract
The Notch signaling Transcription Activation Complex (NTAC) is important for regulation of metazoan tissue differentiation and stem cell homeostasis. NTAC comprises a transcription factor CSL and two co-activators, the Notch receptor intracellular domain (NICD) and the intrinsically disordered Mastermind-like (MAML) protein. NICD has two binding sites for CSL, the short peptide motif RAM and ankyrin repeat domain ANK, which are connected by an intrinsically disordered linker. RAM and ANK interact with CSL at two distant interfaces, forming a bivalent complex in which the ANK-CSL interaction is stabilized by MAML. RAM binds tightly to CSL (KD ∼20nM), but unlike ANK is not required for transcriptional activation.
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